Maintenance of genomes

• Correcting replication errors

• Repairing DNA damage

Maintenance of genomes

• Replication errors

Inserting a wrong nucleotidecausing a mismatch

Inserting or deleting nucleotidescausing helix distortion

Figure 16.3b Genomes 3 (© Garland Science 2007)

Figure 16.4 Genomes 3 (© Garland Science 2007)

An error in replication can cause a point mutation

Maintenance of genomes

• Replication errors

Inserting a wrong nucleotidecausing a mismatch

Inserting or deleting nucleotidescausing helix distortion

Figure 16.5 Genomes 3 (© Garland Science 2007)

Replication slippage in microsatellites

Table 16.1 Genomes 3 (© Garland Science 2007)

Mismatch repair in E. coli

Mismatch repair in E. coli

Maintenance of genomes

• DNA damage

Physical damage – radiation, heat

Hydrolytic damage

Chemical damage – base modifications, base analogs, intercalating agents

Crosslinks caused by UV light

Figure 16.9 Genomes 3 (© Garland Science 2007)

Cyclobutyl dimers and formation of a (6-4) photoproduct caused by UV light

(results in a deletion)

In some organisms photolyases repair crosslinks

In humans the damaged region is excised and re-synthesized

Maintenance of genomes

• DNA damage

Physical damage – radiation, heat

Hydrolytic damage

Chemical damage – base modifications, base analogs, intercalating agents

Hydrolytic damage to bases

Maintenance of genomes

• DNA damage

Physical damage – radiation, heat

Hydrolytic damage

Chemical damage – base modifications, base analogs, intercalating agents

Base analogs and intercalating agents can cause point mutations and insertions/deletions

Figure 16.6c Genomes 3 (© Garland Science 2007)

Various damages to bases

Direct repair of methylated bases

Figure 16.22a Genomes 3 (© Garland Science 2007)

Base excision repair

Base excision repair (removal of uracil)

Fail-safe glycosylases

Table 16.3 Genomes 3 (© Garland Science 2007)

Nucleotide excision repairin E. coli

Short patch repair

Transcription-linked repair

Double-strand break repair(Non-homologous endjoining)

Double-strand breaks arecaused by ionizing radiation

Figure 16.20 Genomes 3 (© Garland Science 2007)

DNA repair processes

Replication-linked repair

SOS repair in E. coli

Expression of Pol IV and Pol V isinduced by DNA damage.

Switching to translesion DNA polymerases

Figure 16.11 Genomes 3 (© Garland Science 2007)

Effect of mutations on gene expression